Alpha-2-adrenoceptors are present on sympathetic nerve terminals (presynaptic) as well as on cells that are innervated by these neurons. Presynaptic alpha-2 adrenoceptors act to limit release of the neurotransmitter, norepinephrine, from the nerves. Recently, three subtypes of alpha-2-adrenoceptors have been described, but the distribution and function of these receptors has not been characterized. During the last year, we have successfully prepared polyclonal antibodies to specific peptides that represent domains of the second extracellular loop that distinguish the differences among these receptors and have shown that the affinity purified antibodies can be used to detect the specific receptor subtypes that have been expressed in transfected COS cells in culture. The antibodies are being used to examine the distribution of the subtypes in brain and in peripheral tissues and to determine if the antibodies will modulate receptor function or reactivity to ligands. Using the antibodies for immunohistochemical reactivity, all three receptor subtypes appear to be present in dorsal root ganglia. In rats subjected to unilateral chronic constriction injury of the sciatic nerve (an animal model of neurogenic pain following injury, perhaps related to reflex sympathetic dystrophy) expression of the alpha-2c-adrenoceptor subtype in the ipsilateral dorsal root ganglia (L4-L5) is increased within 48 hours and persists for at least 3 weeks.